Microcystic Stromal Tumor: A Distinctive Ovarian Sex Cord-Stromal Neoplasm Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and β-catenin Nuclear Expression and CTNNB1 Mutations.

Abstract

Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10+/vimentin+/inhibin-/calretinin- immunophenotype, 3 examples with β-catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and β-catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons 32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT-1/cyclin D1/nuclear β-catenin-positive immunohistochemical profile, which may be useful in diagnosis and in the exclusion of histologic mimics. The presence of diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most supports the classification of MST within the sex cord-stromal category. Aberrant nuclear β-catenin expression, detected in all MSTs, appears to be the result of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of MST and may involve activation of β-catenin with upregulation of cyclin D1.

• Authors: Julie A Irving, Cheng-Han Lee, Stephen Yip, Esther Oliva, W Glenn McCluggage, Robert H Young
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 39 Issue 10 Pg. 1420-6 (Oct 2015) ISSN: 1532-0979 [Electronic] United States
• PMID: 26200099 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CCND1 protein, human
• CTNNB1 protein, human
• DNA-Binding Proteins
• FOXL2 protein, human
• Forkhead Box Protein L2
• Forkhead Transcription Factors
• RNA Splicing Factors
• SF1 protein, human
• Transcription Factors
• WT1 Proteins
• WT1 protein, human
• beta Catenin
• Cyclin D1

Topics

• Adult
• Biomarkers, Tumor (analysis, genetics)
• Cyclin D1 (analysis)
• DNA Mutational Analysis
• DNA-Binding Proteins (analysis)
• Female
• Forkhead Box Protein L2
• Forkhead Transcription Factors (analysis, genetics)
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasms, Cystic, Mucinous, and Serous (chemistry, diagnosis, genetics, pathology)
• Ovarian Neoplasms (chemistry, diagnosis, genetics, pathology)
• RNA Splicing Factors
• Sex Cord-Gonadal Stromal Tumors (chemistry, diagnosis, genetics, pathology)
• Transcription Factors (analysis)
• WT1 Proteins (analysis)
• Wnt Signaling Pathway
• beta Catenin (analysis, genetics)